NEURODEVELOPMENT /NEURODISORDER

该小组的长期目标是建立一个多调查员， 跨学科的研究计划，重点是疾病的 神经系统发育。 这些障碍包括智力迟钝 儿童期发作和成人期发作的学习和行为障碍 发作性精神障碍，其发展基础是强烈的 根据目前的研究文献。 目前的建议是基于以前的和初步的研究，在小鼠 活动领导者和合作者表现出行为和 小鼠的结构性二型性，并建议易感性 这种二态性与传入皮层的发育变化有关， 调节系统 本建议的重点是研究 神经调节性神经递质之间的发育关系 乙酰胆碱[ACh]、去甲肾上腺素[NE]、多巴胺[DA]和血清素[5-羟色胺]。 HT]、性激素和皮质形态发生。 的 我们要检验假设是小鼠的结构性性别差异 大脑皮层和伴随的行为差异， 改变了皮质个体发育的神经调节。 为了验证这一 假设我们将1）评估皮质细胞结构的改变， 雄性和雌性小鼠，通过选择性阻断特异性 神经调节系统的发展;这将需要发展 Hajjii博士的选择性抑制剂化学; 2）确定 神经调质水平和纤维化时间是否存在性别差异 在大脑皮层的个体发育过程中向内生长;（3）测试如何实验 发育过程中激素水平的改变会影响 雄性小鼠与雌性小鼠的神经调质系统; 4）开始研究 性激素和神经调质影响的分子机制 形态发生和随后的行为; 5）开始初步研究，以评估 逆境压力和环境毒素是否会影响 性激素和神经调节化学之间的关系， 行为功能 由于许多发育性发作的CNS疾病影响男性和女性， 差异，阐明大脑性别二型性的个体发生 皮质将帮助我们更好地了解这类疾病的病因。 此外，拟议的研究旨在使 神经障碍/神经发育小组增加研究 能力，基础设施和现有教师的支持，以及 通过增加额外的教师专业知识和扩大研究范围 与其他领域的研究人员一起开发跨学科项目 纪律和机构。

The long-term goal of this group is to establish a multi-investigator, interdisciplinary research program with focus on disorders of the developing nervous system. Such disorders will include mental retardation syndromes, learning and behavioral disorders of childhood onset and adult onset psychiatric disorders for which a developmental basis is strongly suggested by current research literature. The current proposal is based on previous and preliminary studies in mouse by the activity leader and collaborators that have shown behavioral and structural sexual dimorphism in mice and suggested the susceptibility of this dimorphism to developmental alterations in afferent cortical modulatory systems. The focus of the present proposal is to study the developmental relationships between the neuromodulatory neurotransmitters acetylcholine [ACh], norepinephrine [NE], dopamine [DA], and serotonin [5- HT], sex hormones and cortical morphogenesis in this mouse model. The hypothesis we aim to test is that structural sex differences in mouse cerebral cortex and accompanying differences in behavior result from altered neuromodulatory regulation of cortical ontogeny. To test this hypothesis we will 1) assess alterations in cortical cytoarchitecture of male and female mice resulting from selective block of specific neuromodulator systems in development; this will entail the development of selective inhibitors by Dr. Hajjii, Dept. of chemistry; 2) determine whether there are sex differences in neuromodulator level or time of fiber ingrowth during ontogeny of cerebral cortex; (3) test how experimentally altered hormonal levels in development affect the ontogeny of the neuromodulator systems in male versus female mice; 4) begin to study molecular mechanisms through which sex hormones and neuromodulators impact morphogenesis and subsequent behavior; 5) begin a pilot study to assess whether adversive stress and environmental toxins affect the interactions between sex hormones and neuromodulatory chemistry, resulting in altered behavioral function. Since many CNS disorders with developmental onset affect male and females differentially, elucidating the ontogeny of sexual dimorphism in cerebral cortex will help us to better understand the etiology of such disorders. Furthermore, the proposed studies are designed to enable the Neurodisorder/Neurodevelopment group to increase the research capabilities, infrastructure and support for existing faculty as well as expand the research scope by adding additional faculty expertise and by developing interdisciplinary projects with investigators in other disciplines and institutions.